tbuckley/cabot-search huggingface dataset:
Ultrasonography or Radiography for Suspected Pediatric Distal Forearm Fractures
Authors: Peter J. Snelling, Philip Jones, David Bade, Randy Bindra, Joshua Byrnes, Michelle Davison, Shane George, Mark Moore, Gerben Keijzers, Robert S. Ware
Journal: New England Journal of Medicine (2023)

Data on whether ultrasonography for the initial diagnostic imaging of forearm fractures in children and adolescents is noninferior to radiography for subsequent physical function of the arm are limited. Download a PDF of the Research Summary. In this open-label, multicenter, noninferiority, randomized trial in Australia, we recruited participants 5 to 15 years of age who presented to the emergency department with an isolated distal forearm injury, without a clinically visible deformity, in whom further evaluation with imaging was indicated. Participants were randomly assigned to initially undergo point-of-care ultrasonography or radiography, and were then followed for 8 weeks. The primary outcome was physical function of the affected arm at 4 weeks as assessed with the use of the validated Pediatric Upper Extremity Short Patient-Reported Outcomes Measurement Information System (PROMIS) score (range, 8 to 40, with higher scores indicating better function); the noninferiority margin was 5 points. A total of 270 participants were enrolled, with outcomes for 262 participants (97%) available at 4 weeks (with a window of ±3 days) as prespecified. PROMIS scores at 4 weeks in the ultrasonography group were noninferior to those in the radiography group (mean, 36.4 and 36.3 points, respectively; mean difference, 0.1 point; 95% confidence interval [CI], −1.3 to 1.4). Intention-to-treat analyses (in 266 participants with primary outcome data recorded at any time) produced similar results (mean difference, 0.1 point; 95% CI, −1.3 to 1.4). No clinically important fractures were missed, and there were no between-group differences in the occurrence of adverse events. In children and adolescents with a distal forearm injury, the use of ultrasonography as the initial diagnostic imaging method was noninferior to radiography with regard to the outcome of physical function of the arm at 4 weeks. (Funded by the Emergency Medicine Foundation and others; BUCKLED Australian New Zealand Clinical Trials Registry number, ACTRN12620000637943). QUICK TAKE VIDEO SUMMARYUltrasonography for Suspected Pediatric Distal Forearm Fractures 02:08
Care Management Processes Important for High-Quality Diabetes Care
Authors: Kevin A. Peterson, Caroline S. Carlin, Leif I. Solberg, James Normington, Eric F. Lock
Journal: Diabetes Care (2023)

OBJECTIVE Identify the improvement in diabetes performance measures and population-based clinical outcomes resulting from changes in care management processes (CMP) in primary care practices over 3 years. RESEARCH DESIGN AND METHODS This repeated cross-sectional study tracked clinical performance measures for all diabetes patients seen in a cohort of 330 primary care practices in 2017 and 2019. Unit of analysis was patient-year with practice-level CMP exposures. Causal inference is based on dynamic changes in individual CMPs between years by practice. We used the Bayesian method to simultaneously estimate a five-outcome model: A1c, systolic and diastolic blood pressure, guideline-based statin use, and Optimal Diabetes Care (ODC). We control for unobserved time-invariant practice characteristics and secular change. We modeled correlation of errors across outcomes. Statistical significance was identified using 99% Bayesian credible intervals (analogous to P &amp;lt; 0.01). RESULTS Implementation of 18 of 62 CMPs was associated with statistically significant improvements in patient outcomes. Together, these resulted in 12.1% more patients meeting ODC performance measures. Different CMPs affected different outcomes. Three CMPs accounted for 47% of the total ODC improvement, 68% of A1c decrease, 21% of SBP reduction, and 55% of statin use increase: 1) systems for identifying and reminding patients due for testing, 2) after-visit follow-up by a nonclinician, and 3) guideline-based clinician reminders for preventive services during a clinic visit. CONCLUSIONS Effective quality improvement in primary care focuses on practice redesign that clearly improves diabetes outcomes. Tailoring CMP adoption in primary care provides effective improvement in ODC performance through focused changes in diabetes outcomes.
A Roadmap for the Human Gut Cell Atlas
Authors: Matthias Zilbauer, Kylie R. James, Mandeep Kaur, Sebastian Pott, Zhixin Li, Albert Burger, Jay R. Thiagarajah, Joseph Burclaff, Frode L. Jahnsen, Francesca Perrone, Alexander D. Ross, Gianluca Matteoli, Nathalie Stakenborg, Tomohisa Sujino, Andreas Moor, Raquel Bartolome-Casado, Espen S. Bækkevold, Ran Zhou, Bingqing Xie, Ken S. Lau, Shahida Din, Scott T. Magness, Qiuming Yao, Semir Beyaz, Mark Arends, Alexandre Denadai-Souza, Lori A. Coburn, Jellert T. Gaublomme, Richard Baldock, Irene Papatheodorou, Jose Ordovas-Montanes, Guy Boeckxstaens, Anna Hupalowska, Sarah A. Teichmann, Aviv Regev, Ramnik J. Xavier, Alison Simmons, Michael P. Snyder, Keith T. Wilson
Journal: Nature Reviews Gastroenterology & Hepatology (2023)
Safeguarding NICE from patient groups’ conflicts of interest
Authors: Iva Parvanova, Arianna Gentilini, Jonathan Cushing, Huseyin Naci
Journal: BMJ (2023)

Patient groups are essential to understanding the value of medicines, but NICE must improve its disclosure practices for conflicts of interest to ensure credibility and impartiality, write Iva Parvanova, Arianna Gentilini, and colleagues
Inhibition of FGF23 is a therapeutic strategy to target hematopoietic stem cell niche defects in β-thalassemia
Authors: Annamaria Aprile, Laura Raggi, Simona Bolamperti, Isabella Villa, Mariangela Storto, Gaia Morello, Sarah Marktel, Claudio Tripodo, Maria Domenica Cappellini, Irene Motta, Alessandro Rubinacci, Giuliana Ferrari
Journal: Science Translational Medicine (2023)

Clinical evidence highlights a relationship between the blood and the bone, but the underlying mechanism linking these two tissues is not fully elucidated. Here, we used β-thalassemia as a model of congenital anemia with bone and bone marrow (BM) niche defects. We demonstrate that fibroblast growth factor 23 (FGF23) is increased in patients and mice with β-thalassemia because erythropoietin induces FGF23 overproduction in bone and BM erythroid cells via ERK1/2 and STAT5 pathways. We show that in vivo inhibition of FGF23 signaling by carboxyl-terminal FGF23 peptide is a safe and efficacious therapeutic strategy to rescue bone mineralization and deposition in mice with β-thalassemia, normalizing the expression of niche factors and restoring hematopoietic stem cell (HSC) function. FGF23 may thus represent a molecular link connecting anemia, bone, and the HSC niche. This study provides a translational approach to targeting bone defects and rescuing HSC niche interactions, with potential clinical relevance for improving HSC transplantation and gene therapy for hematopoietic disorders.
Constitutive IL-1RA production by modified immune cells protects against IL-1–mediated inflammatory disorders
Authors: Mariasilvia Colantuoni, Raisa Jofra Hernandez, Emanuela Pettinato, Luca Basso-Ricci, Laura Magnani, Grazia Andolfi, Chiara Rigamonti, Annamaria Finardi, Valentina Romeo, Monica Soldi, Lucia Sergi Sergi, Martina Rocchi, Serena Scala, Hal M. Hoffman, Silvia Gregori, Anna Kajaste-Rudnitski, Francesca Sanvito, Luca Muzio, Luigi Naldini, Alessandro Aiuti, Alessandra Mortellaro
Journal: Science Translational Medicine (2023)

Dysregulation of the interleukin-1 (IL-1) pathway leads to immune diseases that can result in chronic tissue and organ inflammation. Although IL-1 blockade has shown promise in ameliorating these symptoms and improving patients’ quality of life, there is an urgent need for more effective, long-lasting treatments. We developed a lentivirus (LV)–mediated gene transfer strategy using transplanted autologous hematopoietic stem/progenitor cells (HSPCs) as a source of IL-1 receptor antagonist (IL-1RA) for systemic delivery to tissues and organs. Transplantation of mouse and human HSPCs transduced with an IL-1RA–encoding LV ensured stable IL-1RA production while maintaining the clonogenic and differentiation capacities of HSPCs in vivo. We examined the efficacy of cell-mediated IL-1RA delivery in three models of IL-1–dependent inflammation, for which treatment hindered neutrophil recruitment in an inducible model of gout, prevented systemic and multi-tissue inflammation in a genetic model of cryopyrin-associated periodic syndromes, and reduced disease severity in an experimental autoimmune encephalomyelitis model of multiple sclerosis. Our findings demonstrate HSPC-mediated IL-1RA delivery as a potential therapeutic modality that can be exploited to suppress tissue and organ inflammation in diverse immune-related diseases involving IL-1–driven inflammation.
Indian Hedgehog release from TNF-activated renal epithelia drives local and remote organ fibrosis
Authors: Eoin D. O’Sullivan, Katie J. Mylonas, Cuiyan Xin, David P. Baird, Cyril Carvalho, Marie-Helena Docherty, Ross Campbell, Kylie P. Matchett, Scott H. Waddell, Alexander D. Walker, Kevin M. Gallagher, Siyang Jia, Steve Leung, Alexander Laird, Julia Wilflingseder, Michaela Willi, Maximilian Reck, Sarah Finnie, Angela Pisco, Sabrina Gordon-Keylock, Alexander Medvinsky, Luke Boulter, Neil C. Henderson, Kristina Kirschner, Tamir Chandra, Bryan R. Conway, Jeremy Hughes, Laura Denby, Joseph V. Bonventre, David A. Ferenbach
Journal: Science Translational Medicine (2023)

Progressive fibrosis is a feature of aging and chronic tissue injury in multiple organs, including the kidney and heart. Glioma-associated oncogene 1 expressing (Gli1
Gene-edited and -engineered stem cell platform drives immunotherapy for brain metastatic melanomas
Authors: Nobuhiko Kanaya, Yohei Kitamura, Maria Lopez Vazquez, Arnaldo Franco, Kok-Siong Chen, Thijs A. van Schaik, Touraj Aligholipour Farzani, Paulo Borges, Toru Ichinose, Waleed Seddiq, Shinji Kuroda, Genevieve Boland, Nusrat Jahan, David Fisher, Hiroaki Wakimoto, Khalid Shah
Journal: Science Translational Medicine (2023)

Oncolytic virus therapy has shown activity against primary melanomas; however, its efficacy in brain metastases remains challenging, mainly because of the delivery and immunosuppressive nature of tumors in the brain. To address this challenge, we first established PTEN-deficient melanoma brain metastasis mouse models and characterized them to be more immunosuppressive compared with primary melanoma, mimicking the clinical settings. Next, we developed an allogeneic twin stem cell (TSC) system composed of two tumor-targeting stem cell (SC) populations. One SC was loaded with oncolytic herpes simplex virus (oHSV), and the other SC was CRISPR-Cas9 gene-edited to knock out nectin 1 (N1) receptor (N1 KO ) to acquire resistance to oHSV and release immunomodulators, such as granulocyte-macrophage colony-stimulating factor (GM-CSF). Using mouse models of brain metastatic BRAF V600E /PTEN −/− and BRAF V600E/wt /PTEN −/− mutant melanomas, we show that locoregional delivery of TSCs releasing oHSV and GM-CSF (TSC-G) activated dendritic cell– and T cell–mediated immune responses. In addition, our strategy exhibited greater therapeutic efficacy when compared with the existing oncolytic viral therapeutic approaches. Moreover, the TSCs composed of SC-oHSV and SC N1KO –releasing GM-CSF and single-chain variable fragment anti–PD-1 (TSC-G/P) had therapeutic efficacy in both syngeneic and patient-derived humanized mouse models of leptomeningeal metastasis. Our findings provide a promising allogeneic SC-based immunotherapeutic strategy against melanomas in the CNS and a road map toward clinical translation.
Children's Oncology Group AALL1331: Phase III Trial of Blinatumomab in Children, Adolescents, and Young Adults With Low-Risk B-Cell ALL in First Relapse
Authors: Laura E. Hogan, Patrick A. Brown, Lingyun Ji, Xinxin Xu, Meenakshi Devidas, Teena Bhatla, Michael J. Borowitz, Elizabeth A. Raetz, Andrew Carroll, Nyla A. Heerema, Gerhard Zugmaier, Elad Sharon, Melanie B. Bernhardt, Stephanie A. Terezakis, Lia Gore, James A. Whitlock, Stephen P. Hunger, Mignon L. Loh
Journal: Journal of Clinical Oncology (2023)

Blinatumomab, a bispecific T-cell engager immunotherapy, is efficacious in relapsed/refractory B-cell ALL (B-ALL) and has a favorable toxicity profile. One aim of the Children's Oncology Group AALL1331 study was to compare survival of patients with low-risk (LR) first relapse of B-ALL treated with chemotherapy alone or chemotherapy plus blinatumomab.
PSMC3 proteasome subunit variants are associated with neurodevelopmental delay and type I interferon production
Authors: Frédéric Ebstein, Sébastien Küry, Victoria Most, Cory Rosenfelt, Marie-Pier Scott-Boyer, Geeske M. van Woerden, Thomas Besnard, Jonas Johannes Papendorf, Maja Studencka-Turski, Tianyun Wang, Tzung-Chien Hsieh, Richard Golnik, Dustin Baldridge, Cara Forster, Charlotte de Konink, Selina M.W. Teurlings, Virginie Vignard, Richard H. van Jaarsveld, Lesley Ades, Benjamin Cogné, Cyril Mignot, Wallid Deb, Marjolijn C.J. Jongmans, F. Sessions Cole, Marie-José H. van den Boogaard, Jennifer A. Wambach, Daniel J. Wegner, Sandra Yang, Vickie Hannig, Jennifer Ann Brault, Neda Zadeh, Bruce Bennetts, Boris Keren, Anne-Claire Gélineau, Zöe Powis, Meghan Towne, Kristine Bachman, Andrea Seeley, Anita E. Beck, Jennifer Morrison, Rachel Westman, Kelly Averill, Theresa Brunet, Judith Haasters, Melissa T. Carter, Matthew Osmond, Patricia G. Wheeler, Francesca Forzano, Shehla Mohammed, Yannis Trakadis, Andrea Accogli, Rachel Harrison, Yiran Guo, Hakon Hakonarson, Sophie Rondeau, Geneviève Baujat, Giulia Barcia, René Günther Feichtinger, Johannes Adalbert Mayr, Martin Preisel, Frédéric Laumonnier, Tilmann Kallinich, Alexej Knaus, Bertrand Isidor, Peter Krawitz, Uwe Völker, Elke Hammer, Arnaud Droit, Evan E. Eichler, Ype Elgersma, Peter W. Hildebrand, François Bolduc, Elke Krüger, Stéphane Bézieau
Journal: Science Translational Medicine (2023)

A critical step in preserving protein homeostasis is the recognition, binding, unfolding, and translocation of protein substrates by six AAA-ATPase proteasome subunits (ATPase-associated with various cellular activities) termed PSMC1-6, which are required for degradation of proteins by 26 S proteasomes. Here, we identified 15 de novo missense variants in the PSMC3 gene encoding the AAA-ATPase proteasome subunit PSMC3/Rpt5 in 23 unrelated heterozygous patients with an autosomal dominant form of neurodevelopmental delay and intellectual disability. Expression of PSMC3 variants in mouse neuronal cultures led to altered dendrite development, and deletion of the PSMC3 fly ortholog Rpt5 impaired reversal learning capabilities in fruit flies. Structural modeling as well as proteomic and transcriptomic analyses of T cells derived from patients with PSMC3 variants implicated the PSMC3 variants in proteasome dysfunction through disruption of substrate translocation, induction of proteotoxic stress, and alterations in proteins controlling developmental and innate immune programs. The proteostatic perturbations in T cells from patients with PSMC3 variants correlated with a dysregulation in type I interferon (IFN) signaling in these T cells, which could be blocked by inhibition of the intracellular stress sensor protein kinase R (PKR). These results suggest that proteotoxic stress activated PKR in patient-derived T cells, resulting in a type I IFN response. The potential relationship among proteosome dysfunction, type I IFN production, and neurodevelopment suggests new directions in our understanding of pathogenesis in some neurodevelopmental disorders.
Transcatheter Repair of Secondary Mitral Regurgitation
Authors: John J.V. McMurray, Marco Metra
Journal: New England Journal of Medicine (2023)

A key question after the publication of the primary results of the COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation)1 was whether the striking reductions in the rate of hospitalization for heart failure and mortality over a period of 24 months would be maintained in the longer term. In this trial, 614 patients with heart failure, a reduced left ventricular ejection fraction, and moderate-to-severe or severe secondary (or functional) mitral regurgitation were randomly assigned in a 1:1 ratio either to undergo transcatheter edge-to-edge repair of the mitral valve in addition . . .
Expanding Treatment for Acute Ischemic Stroke beyond Revascularization
Authors: Jose G. Romano, Tatjana Rundek
Journal: New England Journal of Medicine (2023)

Stroke continues to be a leading cause of disability and death. Although revascularization with thrombolysis and thrombectomy for acute ischemic stroke has had a substantial effect on stroke outcomes, only a limited number of patients with stroke receive these treatments. Moreover, a sizeable proportion of patients treated with thrombolysis do not improve even when treated early. Antiplatelet agents are widely used for the management and prevention of stroke, and they are considered the first-line medication for patients who are not eligible for thrombolysis or starting 24 hours after thrombolysis because these agents reduce the risk of recurrent stroke and cardiovascular . . .
Defining Integrin Tension Required for Chemotaxis of Metastatic Breast Cancer Cells in Confinement
Authors: Young Kim, Le Thi Hong Tram, Kyung Ah Kim, Byoung Choul Kim
Journal: Advanced Healthcare Materials (2023)

Cancer metastasis is affected by chemical factors and physical cues. From cell adhesion to migration, mechanical tension applied to integrin expresses on the cell membrane and physical confinement significantly regulates cancer cell behaviors. Despite the physical interplay between integrins in cells and ligands in the tumor microenvironment, quantitative analysis of integrin tension during cancer cell migration in microconfined spaces remains elusive owing to the limited experimental tools. Herein, a platform termed microconfinement tension gauge tether to monitor spatial integrin tension with single-molecule precision by analyzing the epithelial-growth-factor-induced chemotaxis of metastatic human breast cancer cells in microfluidic channels is developed. The results reveal that the metastatic cancer cells exert the strongest integrin tension in the range of 54-100 pN at the leading edges of cells during chemokinetic migration on a planar surface, while the cells exert the strongest integrin tension exceeding 100 pN at the cell rear when entering microconfinement. Further analysis demonstrates that cells undergo mesenchymal migration under high integrin tension and less confinement, which is converted to amoeboid migration under low integrin tension or high confinement. In summary, the results identify a basic mechanism underlying the mechanical interactions between integrin tension and microenvironment that determines cancer invasion and metastasis.
Interim PET-guided treatment for early-stage NLPHL: a subgroup analysis of the randomized GHSG HD16 and HD17 studies
Authors: Dennis A. Eichenauer, Ina Bühnen, Christian Baues, Carsten Kobe, Helen Kaul, Richard Greil, Alden Moccia, Joseé M. Zijlstra, Bernd Hertenstein, Max S. Topp, Marianne Just, Bastian von Tresckow, Hans-Theodor Eich, Michael Fuchs, Markus Dietlein, Sylvia Hartmann, Andreas Engert, Peter Borchmann
Journal: Blood (2023)
Assessing and Monitoring Nutrition Security to Promote Healthy Dietary Intake and Outcomes in the United States
Authors: Hilary K. Seligman, Ronli Levi, Victoria O. Adebiyi, Alisha Coleman-Jensen, Joanne F. Guthrie, Edward A. Frongillo
Journal: Annual Review of Nutrition (2023)

The US Department of Agriculture's Economic Research Service leads the federal government in data development and research on food security in US households. Nutrition security is an emerging concept that, although closely related, is distinct from food security. No standard conceptualization or measure of nutrition security currently exists. We review the existing research on nutrition security and how it is informed by the more robust literature on food security and diet quality. Based on this review, we propose a conceptual framework for understanding nutrition security and its relationship to food security. We identify two constructs (healthy diets and nutritional status) and multiple subconstructs that form the basis of nutrition security. The proposed framework and corresponding constructs are intended to provide (
Global application of National Comprehensive Cancer Network resource-stratified guidelines for systemic treatment of colon cancer: a population-based, customisable model for cost, demand, and procurement
Authors: Brooke E Wilson, Christopher M Booth, Richard Sullivan, Ajay Aggarwal, Manju Sengar, Susannah Jacob, Freddie Bray, Michael B Barton, Sallie-Anne Pearson
Journal: The Lancet Oncology (2023)
Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints in Cancer Clinical Trials-Innovative Medicines Initiative (SISAQOL-IMI): stakeholder views, objectives, and procedures
Authors: Madeline Pe, Ahu Alanya, Ragnhild Sorum Falk, Cecilie Delphin Amdal, Kristin Bjordal, Jane Chang, Paul Cislo, Corneel Coens, Linda Dirven, Rebecca M Speck, Kristina Fitzgerald, Jayne Galinsky, Johannes M Giesinger, Bernhard Holzner, Saskia Le Cessie, Daniel O'Connor, Kathy Oliver, Vivek Pawar, Chantal Quinten, Michael Schlichting, Jinma Ren, Satrajit Roychoudhury, Martin J B Taphoorn, Galina Velikova, Lisa M Wintner, Ingolf Griebsch, Andrew Bottomley, Cat Bui, Nnadozie Emechebe, Rajesh Kamalakar, Elektra Papadopoulos, Kavita Sail, Rohini Sen, Sean C Turner, Kim Cocks, Jaap Reijneveld, Christoph Gerlinger, Karen Keating, Yun Su, Birgit Wolf, Miaomiao Ge, Anders Ingelgaard, Barbara Peil, Maarten Voorhaar, Brendon Wong, Gracia Dekanic Arbanas, Karin Kuljanic, Duska Petranovic, Ivana Rede, Juan Arraras, Stephen Joel Coons, Sonya Eremenco, Lindsey Murray, Bryce Reeve, Corinne De Vries, Ralf Herold, Francesco Pignatti, Abigirl Machingura, Francesca Martinelli, Jammbe Musoro, Martine Piccart, Jorge Barriuso, Nathan Cherny, Ourania Dafni, Elisabeth De Vries, Bishal Gyawali, Barbara Kiesewetter, Sjoukje Oosting, Felipe Roitberg, Gerhard Rumpold, Felix Schoepf, Michael Tschuggnall, Jennifer Black, Maxime Sasseville, Katherine Soltys, Montserrat Ferrer, Olatz Garin, Gemma Vilagut, Christoph Schürmann, Stefanie Thomas, Beate Wieseler, Claire Snyder, Ariel Alonso Abad, Kris Bogaerts, Febe Brackx, Geert Molenberghs, Geert Verbeke, Cristián Frigolett Catalan, Jan Choi, Doranne Thomassen, Jan Geissler, Willi Sauerbrei, Franziska Gross, Micha Johannes Pilz, Yolanda Barbachano, Lisa Campbell, Khadija Rantell, Gregoire Desplanques, Antoine Regnault, Kate Morgan, Ananda Plate, Silene ten Seldam, Mitsumi Terada, Junki Mizusawa, Sandra Mitchell, Ashley Wilder Smith, Tove Ragna Reksten, Anja Schiel, Kenth Louis Hansen Joseph, Alicyn Campbell, Joseph Cappelleri, Patrizia de Besi, Alexander Russell-Smith, Rickard Sandin, Carla Mamolo, Michael Brundage, Dongsheng Tu, Mogens Groenvold, Morten Petersen, Charlie Cleeland, Lori Williams, Xin Shelley Wang, Jolie Ringash, Melanie Calvert, Samantha Cruz Rivera, Olalekan Lee Aiyegbusi, Els Goetghebeur, Limin Liu, Kelly Van Lancker, Florien Boele, Alexandra Gilbert, Rosemary Peacock, Ethan Basch, Madeleine King, Claudia Rutherford, Vishal Bhatnagar, Mallorie Fiero, Erica Horodniceanu, Laura Lee Johnson, Paul Kluetz, Lisa Rodriguez
Journal: The Lancet Oncology (2023)